The use of antimicrobial agents plays an important part in current medical therapy. This is particularly true in dermatology, where the most effective course of treatment for skin, mucous membranes, hair lesions, or infections frequently includes the use of a topical antimicrobial agent. The present invention includes topical compositions and methods which provide unique performance against a broad spectrum of microbes with excellent speed.
Various carboxylic acids are known to be good antimicrobial agents. However, when these acidic solutions are directly applied to an animal's skin, they may interfere with wound healing, cause irritation, inflammation or the like. Also, these solutions have poor solubility properties in water which, in turn, limits the efficacy of aqueous solutions employing these materials.
It is also well recognized that there is presently a need for a mild antimicrobial or anti-parasitic which can be safely applied to skin and mucous membranes, such as an animal's teats, ears, and eyes, that will be substantially harmless to the applied area but which will eliminate, arrest, or substantially reduce the growth of bacteria, fungi, mold and the like. The instant invention meets this need.
The art discloses that several different carboxylic acid are generally useful in the suppression of fungi, bacteria, molds, and the like growth. U.S. Pat. No. 4,406,884 issued to Fawzi discloses a topical antimicrobial composition in the form of an aqueous gel or lotion. This composition contains C.sub.5 -C.sub.12 fatty acids and has a pH no greater than about 5. U.S. Pat. No. 4,343,798 issued to Fawzi, teaches a topical antimicrobial anti-inflammatory composition having a pH less than about 5 and containing C.sub.5 -C.sub.12 fatty acids together with a corticosteroid component. U.S. Pat. No. 4,489,097 issued to Stone, teaches the addition of anti-fungal/antibacterial materials to sterile compositions. The antifungal/antibacterial material disclosed is a C.sub.4 -C.sub.9 carboxylate antimicrobial agent having a pH of about 6.0 or below. U.S. Pat. No. 4,410,442 issued to Lucas, et al. teaches solutions for use with hydrophilic soft contact lenses containing C.sub.5 -C.sub.12 fatty acids, especially octanoic acid. U.S. Pat. No. 4,392,848 issued to Lucas, et al. teaches a catheter having a liquid reservoir of an antimicrobial agent flowing through the lumen of the catheter. The antimicrobial agent disclosed is a straight-chain carboxylic acid or carboxylic acid salt having a C.sub.4 -C.sub.9 chain. U.S. Pat. No. 4,430,381 issued to Harvey, et al. teaches a process for imparting antimicrobial properties to a material. The antimicrobial being a C.sub.3 -C.sub.12 alkane, alkene or alkyne monocarboxylate. U.S. Pat. Nos. 4,343,788 and 4,479,795, both issued to Mustacich, et al. teach medical polymers that provide diffusion for certain carboxylate antimicrobial agents. U.S. Pat. No. 4,002,775 issued to Kabara teaches a food grade microbicidal composition having a monoester with a C.sub.12 aliphatic fatty acid as its primary microbicide. U.S. Pat. No. 1,772,975 issued to Weiland teaches the use of lactic acid, acetic acid, or combinations thereof, as antiseptics at properly adjusted pH levels. U.S. Pat. No. 2,154,449 issued to Hoffman et al. teaches the use of aliphatic C.sub.3 -C.sub.12 carboxylic acids and their salts as mold inhibitors in food compositions. U.S. Pat. No. 2,190,714 issued to Hoffman, et al. teaches the addition of a C.sub.3 -C.sub.12 carboxylic acid to inhibit growth food products other than margarine and sourdough bread. U.S. Pat. No. 3,404,987 to Kooistra, et al. teaches an antimicrobial containing edible mineral salt and edible acid preservative substances, particularly propionic acid. U.S. Pat. No. 2,466,663 issued to Russ, et al. teaches the use of a topical or intravenous caprylic acid solution to combat mycotic infections or growths. U.S. Pat. No. 2,729,586 issued to Peck teaches a therapeutic composition having at least one salt of a C.sub.3 -C.sub.11 monocarboxylic acid and water soluble chlorophyll.
Other materials also disclose the use of fatty acids for the suppression of fungi, bacteria, mold and the like. Kabara, J., Medium-chain Fatty Acids and Esters as Antimicrobial Agents, Cosmetic and Drug Preservation, Pgs. 275-304, 1984, teaches the use of C.sub.6 -C.sub.22 saturated and unsaturated fatty acids as antimicrobials. Kabara, J., Toxicological, Bactericidal and Fungicidal Properties of Fatty Acids and Some Derivatives, The Journal of the American Oil Chemists' Society, Vol. 56, No. 11, Pages 706A-767A (1979) teaches the applying of fatty acids to animal skin and eyes. Some fatty acids were found to be skin and eye irritants. Kabara, J., Inhibition of Staphylococlus Aureus In a Model Agar-Meat System By Monolaurin: A Research Note, Journal of Food Safety, Vol. 6, Pgs. 197-201 (1984), teaches the use of monolaurin as a food preservative to combat microorganisms. Kabara, J., Antimicrobial Agents Derives from Fatty Acids, JAOCS, Vol. 61, No. 2, Pgs. 397-403 (1984) teaches the use of saturated and unsaturated fatty acids as antimicrobial agents. Kabara, J., GRAS Antimicrobia Agents for Cosmetic Products, Journal of the Society of Cosmetic Chemists, Vol. 31, Pgs. 1-10 (1980), teaches the composition of monolaurin, a phenol, di-tert-butyl anisole, and a chelating agent such as ethylenediaminetetracetic acid to be useful in destroying gram positive and gram negative bacteria. Schemmel, R., Lynch, P., Krohn, K., and Kabara, J., Monolaurin as an Anticaries Agent, teaches the use of glycerol-monolaurin in inhibiting development of smooth surface caries in rats innoculated with Streptococcus mutants. Kabara, Jr., Ohkawa, M., Ikekawa, T., Katori, T., and Mishikawa, Y., Examination on Antitumor, Immunological and Plant-Growth Inhiditory Effects of Monoglycerides of Caprylic, Capric, and Lauric Acids and Related Compounds, Pharacological Effects of Lipids, Volume II, Pgs. 263-272 (1985) teaches the use of the monoglycerides or caprylic, capric and lauric acids for regulating antitumor, immunological, and plant-growth activity. Li, C., and Kabara, J., Effects of Lauricidin on Fomes Annosus and Phellinus Weirii, AOCS Monograph No. 5, Pgs. 45-47 (1978) teaches the use of monolaurin in combating root rot fungi in coniferous forest. Kenney, D., Cosmetic Formulas Preserved With Food-Grade Chemicals, Cosmetics and Toiletries, Part 1, Vol. 97, Pgs. 71-76 (1982) and Kabara, J. and Wernette, C., Cosmetic Formulas Preserved with Food-Grade Chemicals, Cosmetics and Toiletries, Part II, Vol. 97, Pgs. 77-84 (1982) teaches the use of monoglyceride emulsifier, food-grade phenols and a chelator in the preservation of cosmetics. Kabara, J., A New Preservative System For Food, Journal of Food Safety, Volume 4, Pgs. 13-25 (1982) teaches the use of monolaurin, a food grade phenolic, and a chelator as an antimicrobial for the preservation of food. Branan, A. and Davison, P. Antimicrobials in Foods, Marcel Dekker, New York 1983, Pgs. 109-140 teaches the use of saturated, unsaturated and esters of fatty acids as antimicrobials and the use of these compounds for food preservation. Kabara, J., Fatty Acids and Derivatives as Antimicrobial Agents--Review, AOCS Monograph No. 5, Pgs. 1-14 (1978) teaches the use of saturated, unsaturated and esters of fatty acids as antimicrobials and the use of these compounds for permeating microorganism cellular membranes for killing the microorganism.
The art also teaches many methods of ethoxalation. Nonionic Surfactants, Schick, M. J., Marcel Dekken, Inc., New York (1966) and Dillan, K., Effects of the Ethylene Oxide Distribution on Nonionic Surfactant Properties, JAOCS, Vol. 62, No. 7, Pgs. 1144-1151 (1985) teach the ethoxalation of primary alcohols to produce nonionic surfactants. All of the above references herein are incorporated by reference.
The above discussion clearly reflects the ambiguous state of the art with regard to the suitability and selection of fatty acid-based materials as antimicrobials, especially in the topical or preservative mode. The art disclosed materials vary widely in their efficacy and possess an even wider variety of side effects, particularly when employed in veterinary topical materials under adverse or stressful conditions. Many of these materials are also viewed as corrosive. (The term glyceryl and glycerol are used interchangeably herein when describing fatty acid esters.)